Summary
This laboratory-based study characterised protective and pathogenic antibody responses from a Shigella flexneri outbreak in non-human primates to inform vaccine development. Key findings include significant affinity maturation of O-antigen-targeting antibodies with cross-serotype reactivity, and a counterintuitive discovery that antibodies against type III secretion system proteins can either inhibit or enhance virulence depending on their epitope specificity. These mechanistic insights provide evidence-based guidance for rational immunogen selection in Shigella vaccine design.
UK applicability
Shigella epidemiology and antimicrobial resistance patterns differ between the United Kingdom and the source population (non-human primates in a US facility); however, the structural and immunological mechanisms identified may be broadly applicable to vaccine development efforts globally, including UK-relevant vaccine research programmes.
Key measures
Monoclonal antibody affinity maturation (>10% cross-reactivity gain); T cell and antibody response magnitude to T3SS proteins (IpaD, IpaB); bacterial virulence inhibition or enhancement in vitro and in vivo depending on epitope specificity
Outcomes reported
The study isolated and characterised monoclonal antibodies against Shigella candidate vaccine antigens from an outbreak in a non-human primate research facility, examining their protective or pathogenic potential. It measured antibody affinity maturation, cross-reactivity across serotypes, and the ability of antibodies targeting T3SS proteins to either inhibit or enhance bacterial virulence in vitro and in vivo.
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